Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects

Abstract

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-β-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-β-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-β-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het.

Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases

“…To our knowledge, research on the amorphization of hesperidin can be considered as one of the pioneering processes to improve its solubility. For example, Wei et al obtained amorphous hesperidin using the wetness impregnation method [ 21 , 22 ], Wdowiak et al obtained amorphous inclusion complex by solvent evaporation [ 23 ]. Nevertheless, other techniques have been widely used to improve the solubility of hesperidin [ 15 ].…”

A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro

“…Enhancement of the water solubility and antioxidant activity have been reported on hesperidin mixed with chitooligosaccharide [ 13 ]. It has also been reported that inclusion complexes of hesperidin or hesperetin with hydroxypropyl β-cyclodextrin increase solubility and antioxidant potential [ 14 ]. Glycosylation of hesperidin or hesperetin has been studied and is considered an efficient and promising method to increase solubility and bioavailability [ 15 , 16 , 17 ].…”

Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment

“…Corciova et al [ 63 ] also reported that complexing hesperidin with HP-β-CD resulted in improved dissolution as well as antioxidant and antibacterial properties. Similarly, complexing hesperetin with β-CD and HP-β-CD enhances the dissolution rate and improves solubility, along with anti-inflammatory and cytotoxicity effects on cancer cell lines [ 64 , 65 , 66 ].…”